Hepatitis B, Chronic, Hepatitis D, Chronic
Conditions
Keywords
Hepatitis D, Hepatitis B
Brief summary
The objective of this study is to determine the effectiveness of peginterferon alfa-2b 1.5 mcg/kg/week administered for 52 weeks (wk) in previously untreated participants coinfected with hepatitis virus B and D. After 52-week treatment and 52-week follow-up, the virologic, biochemical, and histological response will be evaluated.
Interventions
BIOLOGICALPeginterferon alfa-2b (PegIntron, SCH 54031)
Peginterferon alfa-2b 1.5 mcg/kg/wk subcutaneously (SC) for 52 weeks.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Participants must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent. * Age 18-65 years old. * HBsAg positive \>6 months. * ALT \>= 2 ULN \>6 months. * HDV RNA positive serology. * Serum antibody to hepatitis delta antigen of IgG and IgM class. * Knodell score HAI \>= 6 and F \>= 0; positive test for intrahepatic Delta antigen in liver biopsy. * Women of childbearing potential (includes women who are less than 1 year postmenopausal and women who become sexually active) must be using an acceptable method of birth control (e.g., hormonal contraceptive, medically prescribed IUD, condom in combination with spermicide) or be surgically sterilized (e.g., hysterectomy or tubal ligation). * Participants must be free of any clinically significant disease (other than chronic hepatitis B and D), that would interfere with study evaluations. * Participants must understand and be able to adhere to the dosing and visit schedules, and agree to record symptom severity scores, medication times, concomitant medications, and adverse events accurately and consistently in a daily diary.
Exclusion criteria
* Age \<18 and \>65. * Concomitant HCV and/or HIV infection. * Actual liver failure (total serum bilirubin \>2.5 x normal, prolonged prothrombin time \>3 sec, serum albumin \<3 g/dl, history of ascites, variceal bleeding, or hepatic encephalopathy). * Toxic or autoimmune hepatitis (ANA titers \> 1:160), metabolic liver diseases (Wilson disease, hemochromatosis, α-1 antitrypsin deficiency) * Women who are pregnant or nursing. * Leukopenia (\<2500/mm\^3), neutropenia (\<1000/mm\^3), hemoglobin \<10 g/dl, presence of other severe diseases (myocardiopathy, diabetes mellitus, arterial hypertension, neoplasia, neurologic diseases, malnutrition). * Antiviral, immunomodulatory, corticosteroid, or chemotherapeutical treatment within 6 months of the participation in the study. * Depression and/or psychiatric disorders.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Virological Response | 52 weeks (end of treatment [EOT]), 104 weeks (end of follow-up [EOF]) following treatment initiation | For virological response, a participant was defined as a responder if his/her serum sample tested negative for Hepatitis D Virus - ribonucleic acid (HDV-RNA) by polymerase chain reaction (PCR) at end of treatment (EOT). |
| Number of Participants With a Biochemical Response | 52 weeks (EOT), 104 weeks (EOF) | A participant was defined as a responder if his alanine aminotransferase (ALT) level after 52 weeks, i.e. at EOT, was below the upper reference range as specified by Bioclinica. The normal reference range for ALT is 5-55 U/L. |
| Number of Participants With a Combined Response | 52 weeks (EOT), 104 weeks (EOF) | The combined response was defined as an ALT level below the upper reference range and a negative HDV-RNA test. The normal reference range for ALT is 5-55 U/L. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Hepatitis B Virus (HBV) Replication Response (HBV Response) | 52 week (EOT) | Serum samples collected from the participants were tested by PCR to detect HBV-DNA. HBV response was defined as the absence of HBV-deoxyribonucleic acid (HBV-DNA) in serum. |
| Number of Participants With a Liver Histology Response | Baseline and 52 week (EOT) | The liver histology response was defined as at least a 2 point decrease in the necrosis inflammation score (a sum of periportal necrosis \[0-10\], lobular inflammation \[0-4\], portal inflammation \[0-4\], with the total score of 18 representing the worst outcome) and no increase or regression of fibrosis (scored \[0-4\]) in the pre- and post-treatment liver biopsies. The efficacy of treatment based on histological response was assessed by the investigator as complete response, partial response, minimal response, progressive disease, and not assessable at EOT. |
Participant flow
Pre-assignment details
Of the enrolled participants, 19 received no study medication and 1 was not eligible. The Intent-to-Treat (ITT) population is 48.
Participants by arm
| Arm | Count |
|---|---|
| PegIntron Peginterferon alfa-2b 1.5 mcg/kg/wk SC for 52 weeks | 48 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 12 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | PegIntron |
|---|---|
| Age, Continuous | 37.55 years STANDARD_DEVIATION 12.48 |
| Region of Enrollment Romania | 48 Participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 47 / 49 |
| serious Total, serious adverse events | 3 / 49 |
Outcome results
Primary
Number of Participants With a Biochemical Response
A participant was defined as a responder if his alanine aminotransferase (ALT) level after 52 weeks, i.e. at EOT, was below the upper reference range as specified by Bioclinica. The normal reference range for ALT is 5-55 U/L.
Time frame: 52 weeks (EOT), 104 weeks (EOF)
Population: The population analyzed excluded participants that were not administered study medication, had protocol violations and those for whom ALT values were not available.~2 participants with adverse events (AE) that had protocol violations have been included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PegIntron | Number of Participants With a Biochemical Response | Responders at 52 weeks | 18 Participants |
| PegIntron | Number of Participants With a Biochemical Response | Non-responders at 52 weeks | 14 Participants |
| PegIntron | Number of Participants With a Biochemical Response | Responders at 104 weeks | 9 Participants |
| PegIntron | Number of Participants With a Biochemical Response | Non-responders at 104 weeks | 23 Participants |
Primary
Number of Participants With a Combined Response
The combined response was defined as an ALT level below the upper reference range and a negative HDV-RNA test. The normal reference range for ALT is 5-55 U/L.
Time frame: 52 weeks (EOT), 104 weeks (EOF)
Population: The population analyzed excluded participants that were not administered study medication, had protocol violations and those for whom ALT values were not available.~2 participants with adverse events (AE) that had protocol violations have been included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PegIntron | Number of Participants With a Combined Response | Responders at 52 weeks | 7 Participants |
| PegIntron | Number of Participants With a Combined Response | Non-responders at 52 weeks | 25 Participants |
| PegIntron | Number of Participants With a Combined Response | Responders at 104 weeks | 6 Participants |
| PegIntron | Number of Participants With a Combined Response | Non-responders at 104 weeks | 26 Participants |
Primary
Number of Participants With a Virological Response
For virological response, a participant was defined as a responder if his/her serum sample tested negative for Hepatitis D Virus - ribonucleic acid (HDV-RNA) by polymerase chain reaction (PCR) at end of treatment (EOT).
Time frame: 52 weeks (end of treatment [EOT]), 104 weeks (end of follow-up [EOF]) following treatment initiation
Population: The population analyzed excludes participants that were not administered any study medication and had protocol violations. 2 participants with adverse events (AE) that had protocol violations have been included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PegIntron | Number of Participants With a Virological Response | Responders at 52 weeks | 12 Participants |
| PegIntron | Number of Participants With a Virological Response | Non-responders at 52 weeks | 24 Participants |
| PegIntron | Number of Participants With a Virological Response | Responders at 104 weeks | 9 Participants |
| PegIntron | Number of Participants With a Virological Response | Non-responders at 104 weeks | 27 Participants |
Secondary
Number of Participants With a Liver Histology Response
The liver histology response was defined as at least a 2 point decrease in the necrosis inflammation score (a sum of periportal necrosis \[0-10\], lobular inflammation \[0-4\], portal inflammation \[0-4\], with the total score of 18 representing the worst outcome) and no increase or regression of fibrosis (scored \[0-4\]) in the pre- and post-treatment liver biopsies. The efficacy of treatment based on histological response was assessed by the investigator as complete response, partial response, minimal response, progressive disease, and not assessable at EOT.
Time frame: Baseline and 52 week (EOT)
Population: The population analyzed excludes participants that were not administered any study medication and had protocol violations. 2 participants with adverse events (AE) that had protocol violations have been included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PegIntron | Number of Participants With a Liver Histology Response | Complete response | 10 Participants |
| PegIntron | Number of Participants With a Liver Histology Response | Partial response | 14 Participants |
| PegIntron | Number of Participants With a Liver Histology Response | Minimal response | 6 Participants |
| PegIntron | Number of Participants With a Liver Histology Response | Progressive disease | 3 Participants |
| PegIntron | Number of Participants With a Liver Histology Response | Response not assessable | 3 Participants |
Secondary
Number of Participants With Hepatitis B Virus (HBV) Replication Response (HBV Response)
Serum samples collected from the participants were tested by PCR to detect HBV-DNA. HBV response was defined as the absence of HBV-deoxyribonucleic acid (HBV-DNA) in serum.
Time frame: 52 week (EOT)
Population: The population analyzed excludes participants that were not administered any study medication and had protocol violations. 2 participants with adverse events (AE) that had protocol violations have been included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PegIntron | Number of Participants With Hepatitis B Virus (HBV) Replication Response (HBV Response) | Responders | 6 Participants |
| PegIntron | Number of Participants With Hepatitis B Virus (HBV) Replication Response (HBV Response) | Non responders | 30 Participants |